The goal of the proposed research is to understand the molecular mechanism of action of the opiate receptor and to gain insight into general principles of receptor functioning. The opiate receptor is an integral membrane-bound proteinaceous structure present in mammalian nervous system tissue and provides the site of action for opiates and also for endogenous peptides which may function as neurotransmitters or hormones involved in pain perception. The molecular properties of the opiate receptor will be examined as a solubilized entity or in membrane fragments that are highly enriched in the receptor protein. The details of the mode of action of the opiate receptor with regard to both opiates and endogenous substrates will be attacked by biophysical techniques. In particular, evidence will be sought on the molecular level for a ligand-induced conformational change, which is strongly supported by phenomenonological evidence. It is hoped that the elucidation of the properties and mechanism of the opiate receptor will lead to an understanding of drug addiction on the cellular level. At the same time biophysical approaches to bacterial receptor systems will be further developed in terms of sophistication and broadness of application. It is hoped that elucidation of the molecular mechanisms of sensory perception in bacteria will provide a model for such processes in mammals.